Evidence map›Paper›PMID 38370611›Full record

ArticlebioRxiv : the preprint server for biology2024

Substrate recognition principles for the PP2A-B55 protein phosphatase.

Thomas Kruse, Dimitriya H Garvanska, Julia Varga, William Garland, Brennan McEwan, Jamin B Hein, Melanie Bianca Weisser, Iker Benavides Puy, Camilla Bachman Chan, Paula Sotelo Parrila and 6 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 3 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 7 institutions in 5 countries.

Thomas KruseNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
Dimitriya H GarvanskaNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
Julia VargaDepartment of Microbiology and Molecular Genetics, Institute for Biomedical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, 9112001, Israel.
William GarlandDepartment of Molecular Biology and Genetics, Universitetsbyen 81, Aarhus University, Aarhus, Denmark.ORCID 0000-0001-5167-8004
Brennan McEwanBiochemistry and Cell Biology, Geisel School of Medicine at Dartmouth College, Hanover, NH, USA.
Jamin B HeinNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
Melanie Bianca WeisserNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
Iker Benavides PuyNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
Camilla Bachman ChanNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
Paula Sotelo ParrilaGene Center Munich, Ludwig-Maximilians- Universität München, Munich, 81377, Germany.
Blanca Lopez MendezNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
Jeyaprakash ArulanandamGene Center Munich, Ludwig-Maximilians- Universität München, Munich, 81377, Germany.ORCID 0000-0002-1889-8635
Ora Schueler-FurmanDepartment of Microbiology and Molecular Genetics, Institute for Biomedical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, 9112001, Israel.
Torben Heick JensenDepartment of Molecular Biology and Genetics, Universitetsbyen 81, Aarhus University, Aarhus, Denmark.
Arminja KettenbachBiochemistry and Cell Biology, Geisel School of Medicine at Dartmouth College, Hanover, NH, USA.
Jakob NilssonNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
Novo Nordisk Foundation · DKAarhus University · DKDartmouth College · USHebrew University of Jerusalem · ILLudwig-Maximilians-Universität München · DEUniversity of Copenhagen · DKWellcome Centre for Cell Biology · GB

Funding

Phosphorylation Signaling by Phosphoprotein PhosphatasesR35GM119455 · NIGMS · DARTMOUTH COLLEGE · PI Arminja Nadine Kettenbach · 2016 to 2026
$5.1M
NIGMS NIH HHS R35 GM119455Wellcome Trust
6 · The paper itself

Abstract

The PP2A-B55 phosphatase regulates a plethora of signaling pathways throughout eukaryotes. How PP2A-B55 selects its substrates presents a severe knowledge gap. By integrating AlphaFold modelling with comprehensive high resolution mutational scanning, we show that α-helices in substrates bind B55 through an evolutionary conserved mechanism. Despite a large diversity in sequence and composition, these α-helices share key amino acid determinants that engage discrete hydrophobic and electrostatic patches. Using deep learning protein design, we generate a specific and potent competitive peptide inhibitor of PP2A-B55 substrate interactions. With this inhibitor, we uncover that PP2A-B55 regulates the nuclear exosome targeting complex by binding to an α-helical recruitment module in RBM7. Collectively, our findings provide a framework for the understanding and interrogation of PP2A-B55 in health and disease.

Identifiers

PMID38370611
PMCPMC10871369
OpenAlexW4391750695

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.